A central theme of this proposal will be the use of methods for protein analysis, down to the level of primary structure, to identify or recognize populations of lymphoid cells apparently finely differentiated with respect to a particular Ig product which they or their progeny can secrete. The tissue origins, traffic, "homing", interaction with other cells and cell products, and potentials of their progeny will be assessed for some of the lymphoid cell populations singled out. Fine structural analysis of parts of an Ig product, such as the SC found in rabbit sIgA, will be continued with aims being to better understand the "homing" of IgA precursor lymphocytes and the process by which the IgA products of their daughter plasma cells are blended into exocrine secretions. Now that primary structural analysis of hyper-variable regions of antibodies raised in guinea pigs has been achieved, it has become feasible to use sequences which determine hapten-binding specificity as the most definitive markers for particular lymphoid cell populations clones. Since it appears that inbred guinea pigs have a limited structural gene pool for VH regions with a given hapten-binding specificity, it will probably be possible to detect various appropriately but alternatively differentiated populations/clones of plasma cells by their contributions to a circulating antibody pool. Thus we aim to ask, in as definitive a way as possible, how Ir genotype, manipulation of the immune response with respect to class of antibody, induction of an unresponsiveness in the T-cell population, induction of tolerance in the B-cell population, suppression of idiotype and potentiation of the immune response with allogeneic cells may affect which clones of cells which and dominate upon antigenic challenge and which are absent or do not proliferate and thus fail to contribute much to the antibody pool.